The goal of this research is to define the relative roles of intra-and extra-mitochondrial genetic systems in determining cellular and mitochondrial phenotype. Our object is to determine molecular principles by which information in mitochondrial DNA influences differentiation. Particular emphasis will be placed on analyzing the regulation of mitochondrial biogenesis. We propose to apply both genetic and biochemical techniques to this end. Yeast mutants defective in porphyrin and cytochrome biosynthesis will be employed to determine how information required for regulating delta-amino-levulinate (Alv) formation is transmitted between mitochondrial and nuclear genes. Methods selective for non-Mendelian, point mutations will be used to obtain mutants specifically controlling porphyrin biosynthesis. The degree of control exerted by porphyrin supply on mitochondrial number, composition and structure will be assessed with mutants requiring exogenous Alv. This will be accomplished by growing mutants in different concentrations of Alv, examining structure with the electron microscope, and determining enzymatic and chemical composition of isolated mitochondria.